A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in subjects with prostate cancer Journal Article


Authors: Slovin, S. F.; Kehoe, M.; Durso, R.; Fernandez, C.; Olson, W.; Gao, J. P.; Israel, R.; Scher, H. I.; Morris, S.
Article Title: A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in subjects with prostate cancer
Abstract: PSMA-VRP is a propagation defective, viral replicon vector system encoding PSMA under phase I evaluation for patients with castration resistant metastatic prostate cancer (CRPC). The product is derived from an attenuated strain of the alphavirus, Venezuelan Equine Encephalitis (VEE) virus, and incorporates multiple redundant safety features. In this first in human trial, two cohorts of 3 patients with CRPC metastatic to bone were treated with up to five doses of either 0.9×107IU or 0.36×108IU of PSMA-VRP at weeks 1, 4, 7, 10 and 18, followed by an expansion cohort of 6 patients treated with 0.36×108IU of PSMA-VRP at weeks 1, 4, 7, 10 and 18. No toxicities were observed. In the first dose cohort, no PSMA specific cellular immune responses were seen but weak PSMA-specific signals were observed by ELISA. The remaining 9 patients, which included the higher cohort and the extension cohort, had no PSMA specific cellular responses. PSMA-VRP was well-tolerated at both doses. While there did not appear to be clinical benefit nor robust immune signals at the two doses studied, neutralizing antibodies were produced by both cohorts suggesting that dosing was suboptimal. © 2012 Elsevier Ltd.
Keywords: prostate cancer; immunotherapy; vaccine; psma; vee; vrp
Journal Title: Vaccine
Volume: 31
Issue: 6
ISSN: 0264-410X
Publisher: Elsevier Inc.  
Date Published: 2013-01-30
Start Page: 943
End Page: 949
Language: English
DOI: 10.1016/j.vaccine.2012.11.096
PROVIDER: scopus
PUBMED: 23246260
DOI/URL:
Notes: --- - "Export Date: 1 February 2013" - "CODEN: VACCD" - "Source: Scopus"
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MSK Authors
  1. Susan Slovin
    197 Slovin
  2. Howard Scher
    900 Scher